Using quantitative autoradiography, we will characterize altered regional brain physiology and metabolism in a murine model of focal herpes simplex virus (HSV) encephalitis. Using radiolabeled metabolic tracers injected in vivo and computerized image analysis of brain section autoradiograms, we will examine regional uptake of antiviral pyrimidine nucleosides (14C-FMAU, 14C-FIAC and 125I-FIAC), glucose utilization (14C-2-deoxyglucose), blood-brain barrier permeability (14C-alpha-aminoisobutyric acid and 14C-sucrose), tissue pH (14C-DMO), and antiviral antibody sequestration (125I-labeled monoclonal antibody). Contributions of both viral infection and secondary host immune and inflammatory responses to the metabolic derangements will be assessed within infected regions as well as in uninfected brain structures. These results will provide unique information bearing on the pathogenesis of neurologic dysfunction accompanying HSV encephalitis and hopefully also lead to new, more effective diagnositc and therapeutic strategies in man.